tbuckley/cabot-search huggingface dataset:
Clinical and radiological predictors of organ preservation in patients with rectal cancer treated with total neoadjuvant therapy.
Authors: Jonathan B Yuval, Floris S Verheij, Sabrina T. Lin, Hannah M Thompson, Dana M Omer, Jin K Kim, Jesse Joshua Smith, Marc J Gollub, Li-Xuan Qin, Julio Garcia-Aguilar
Journal: Journal of Clinical Oncology (2022)

3619 Background: Baseline rectal MRI is routinely used for tumor staging, selecting the initial treatment and prognostication of patients with rectal adenocarcinoma. However, associations of baseline clinical and MRI variables with organ preservation (OP) in a prospective randomized trial have not been reported. Methods: Patients with MRI staged clinical stage II or III rectal adenocarcinoma treated in a prospective phase II clinical trial were randomized to either induction chemotherapy (FOLFOX or CAPEOX) followed by chemoradiation or chemoradiation followed by consolidation chemotherapy (FOLFOX or CAPEOX) and recommended total mesorectal excision (TME) or watch-and-wait (WW) based on clinical response. The primary outcome was OP, defined as the time from randomization to the clinical decision of TME or last follow-up, whichever occurred first. Clinical variables included: age, sex, race, tumor grade, radiation dose and treatment arm. Radiological variables (evaluated by baseline MRI prior to randomization) included: distance from the anal verge, tumor length, clinical T stage, clinical N stage, relationship to the mesorectal fascia, presence of extramural vascular invasion (EMVI) and mucinous radiographic findings (&gt;50%). Associations of OP with clinical and radiological variables were assessed utilizing the Cox regression model in univariate and multivariate settings. The final multivariate model was chosen using backward selection. Results were analyzed by intention to treat. Results: Case report forms (CRFs) from baseline MRI were available for 289 of 324 randomized patients (89%). Patients with CRFs differed from those without CRFs in race, distance of the tumor from the anal verge and clinical T stage. Median follow-up was 3.4 years. A total of 156 of 324 patients were recommended TME during the study period. The 3-year OP rate was 47%. Independent predictors of OP in the multivariate analysis can be seen in the table. Conclusions: Although the patients included in this analysis may not be fully representative of the entire cohort, our data shows that several radiological variables associated with unfavorable tumor biology – tumor involvement of the mesorectal fascia, presence of EMVI and involved mesorectal nodes – were negatively associated with organ preservation. This information will be useful in selecting rectal cancer patients for WW and should be used for patient stratification in future clinical trials. Clinical trial information: NCT02008656. [Table: see text]
Incidence, predictors and outcomes of cardiovascular events in patients with chronic lymphocytic leukemia.
Authors: Ghulam Ghous, Nanuli Gvazava, Peter Egwom, Mohammad Saleh, Diana Franco, Hafiz Muhammad Hassan Shoukat, Pak Ho Au, Kelechi Nwabara, Zahid Tarar
Journal: Journal of Clinical Oncology (2022)

e19524 Background: CLL accounts for about one-quarter of the new cases of leukemia and affects mainly elderly population. Recent literature highlights increased cardiovascular events in patients with CLL, notably those being treated with targeted therapy such as Bruton tyrosine kinase inhibitors. Here we examine data obtained from the National Inpatient Sample to find out incidence, predictors and outcomes of cardiovascular events in patients with CLL. Methods: We analyzed the National inpatient database from year 2019 and extracted the data of all patients with CLL. Multivariate regression analysis was performed to determine the aforementioned outcomes in CLL patients. Results: CLL patients showed increased odds of all cause in-hospital mortality (Adjusted Odds ratio (AOR) 1.28, 95% CI 1.19-1.38, P&lt;0.001) in comparison to general adult population. CLL patients had higher odds of developing Atrial fibrillation (AOR 1.11, 95% CI 1.06-1.15 P &lt;0.001) compared to patients without CLL. CLL patients had significantly higher odds of cardiac tamponade and pericardial effusion (AOR 1.64, 95% CI 1.10-2.42, P&lt;0.001, 1.65 95% CI 1.43-1.92, P&lt;0.001) respectively. Odds of congestive heart failure (AOR 0.97, 95% CI 0.93-1.01, P0.10) and atrial flutter (AOR 1.03, 95% CI 0.93-1.17, P 0.55) were similar between CLL patients and general adult populations. Patients with CLL have Increased mean hospital length of stay (adjusted mean LOS 0.51, 95% CI 0.42-0.61, p&lt;0.001) and mean total hospital charges (adjusted mean charges 2006$, 95% CI 173$-3840$, P 0.03). [Table] We investigated the predictors of inpatient mortality in CLL patients and found that increase in age, black race, acute kidney injury, alcohol use, malnutrition and weekend admissions were associated with higher odds of mortality, whereas smoking, obesity, and female gender showed lower odds of mortality. Conclusions: CLL patients are at increased risk of developing atrial fibrillation, pericardial effusion, pericardial tamponade and all-cause in hospital mortality compared to their non-CLL counterparts, even after accounting for variables such as age, gender etc. Moreover, CLL patients have higher inpatient mortality associated with certain factors such as age progression, AKI, black race, alcohol abuse and malnutrition. Patients should be referred to cardiologist early and cardiovascular status should be optimized especially before initiating targeted therapy.[Table: see text]
68Ga-PSMA PET SUVmax predicts gleason pattern 4 at biopsy in intermediate risk prostate cancer
Authors: A. Xue, A.A. Kalapara, Z.E. Ballok, S.M. Levy, D. Sivaratnam, D. Moon, J.P. Grummet, M.F. Frydenberg
Journal: European Urology (2022)
MEDB-85. Transcriptional complexes as resistance drivers to BET inhibition
Authors: Adam Boynton, Leslie Lupien, Rushil Kumbhani, Gabrielle Gionet, Madison Chacon, Amy Goodale, David Root, Hasmik Keshishian, Margaret Robinson, Steven Carr, Pratiti Bandopadhayay
Journal: Neuro-Oncology (2022)

Abstract BET-bromodomain inhibition (BETi) is a promising therapeutic strategy to target MYC-driven cancers, including Group 3 medulloblastoma, a deadly childhood brain tumor. We have shown that BET inhibitors exhibit preclinical efficacy against MYC¬-amplified medulloblastoma, providing motivation to evaluate this drug class in early phase clinical trials. However, our work has also found that MYC-amplified medulloblastoma cells can acquire resistance to BETi, suggesting that curative responses for this disease will require combination therapy. To guide the development of such combination therapies, we have focused our efforts on elucidating the mechanisms through which medulloblastoma cells acquire resistance to BETi. We found that medulloblastoma cells can develop tolerance to BETi by reinstating the expression of cell-essential “rescue genes,” which include bHLH transcription factors, cell-cycle regulators, and anti-apoptosis genes. This transition to the resistant cell state is mediated through changes in chromatin structure including the upregulation of H3K4me3 promoters. Our preliminary results suggest that BETi-resistant cells maintain mRNA transcription and protein translation of important mediators of resistance. Importantly, we observe that BETi-resistant medulloblastoma cells are more dependent on specific protein complexes involved in transcriptional regulation. This project explores the mechanisms through which these transcriptional regulators help maintain transcription of rescue genes that drive BETi resistance and evaluates the potential of targeting these drivers of BETi resistance. These results will help guide the development of combination approaches to improve the efficacy of BETi for the treatment of MYC-driven medulloblastoma.
Trial in progress update on ENGOT-cx8/GOG-3024/innovaTV 205: Addition of a new cohort with first-line (1L) tisotumab vedotin (TV) + pembrolizumab (pembro) + carboplatin (carbo) ± bevacizumab (bev) in recurrent/metastatic cervical cancer (r/mCC).
Authors: Ignace Vergote, Mansoor Raza Mirza, Jalid Sehouli, Domenica Lorusso, Fatih Köse, David Cibula, Anneke M. Westermann, Dearbhaile Catherine Collins, Susana N. Banerjee, Ana Oaknin, Ibrahima Soumaoro, Shweta Jain, Bradley J. Monk
Journal: Journal of Clinical Oncology (2022)

TPS5603 Background: Despite the use of platinum-taxane doublets ± bev in eligible patients (pts), overall survival (OS) outcomes for pts with r/mCC remain poor. With the US approval of pembro + chemotherapy ± bev in the 1L setting for r/mCC with ≥1% of programmed death ligand 1–positive cells in the tumor, an unmet need remains for pts who do not meet this threshold and for pts who progress or are intolerant to standard treatment (tx). TV is a tissue factor–directed antibody–drug conjugate that has been granted accelerated approval in the United States for the tx of adults with r/mCC with disease progression on or after chemotherapy. To develop more effective treatments, we investigated TV in combination with agents with known activity in cervical cancer. We conducted a 2-part, multicohort phase 1b/2 trial, ENGOT-cx8/GOG-3024/innovaTV 205 (NCT03786081), to evaluate TV in combination with bev, pembro, or carbo. The phase 1b dose-escalation phase of innovaTV 205 established the recommended phase 2 dose (RP2D) and the feasibility of these doublet combinations (Monk et al, IGCS 2021). Moreover, we recently reported encouraging antitumor activity from the dose-expansion cohort of TV + carbo (1L; confirmed objective response rate [ORR], 55%; median duration of response [DOR], 8.3 mo) and TV + pembro (second-line; confirmed ORR, 38%; median DOR, 13.8 mo) (Vergote et al, ESMO 2021). The current report describes the design of a new, ongoing dose expansion cohort in the innovaTV 205 study to evaluate the combinations of TV, pembro, and carbo ± bev. Methods: A new cohort has been added to the innovaTV 205 study, comprising adult pts with recurrent or stage IVB squamous, adenosquamous, or adenocarcinoma of the cervix with no prior systemic therapy and an Eastern Cooperative Oncology Group score of 0 or 1. Pts will be treated with the RP2D of TV (2.0 mg/kg) + carbo (AUC 5 mg/mL), pembro (200 mg), and bev (15 mg/kg) every 3 weeks or with TV + carbo (AUC 5 mg/mL) and pembro (200 mg). To assess the regimen’s initial tolerability, there will be a dose-limiting toxicity evaluation period that will consist of completion of 1 tx cycle of 21 days for 6 pts enrolled to receive the quadruplet combination. The primary endpoint of this dose expansion phase is confirmed ORR per RECIST v1.1; secondary endpoints include DOR, time to response, progression-free survival, OS, and safety. Enrollment is ongoing in the United States and Europe, with additional sites planned globally. Clinical trial information: NCT03786081.
Effects of high-fat and low-carbohydrate diet combined with radiation therapy on tumor microenvironment in LLC tumor-bearing mice.
Authors: Ling Xiao, Tao Li
Journal: Journal of Clinical Oncology (2022)

e20543 Background: Metabolic reprogramming of tumor immune cells can regulate immune function. To add a sentence linking tumor metabolism with radioimmunity. In this study, the high heterogeneity and reprogramming of tumor cell metabolism were utilized to explore the effects of high fat and low carbohydrate diet combined with radiotherapy on tumor immune microenvironment of tumor mice bearing LLC from the perspective of tumor microenvironment. Methods: Lewis lung cancer (LLC) model was established in female C57BL/6J mice aged 6 to 8 weeks and around 18g, and they were given a high fat and low carbohydrate diet (45F, fat 45.00% of energy) combined with radiotherapy. The body weight, tumor growth, blood glucose and blood ketone (βHB) values, survival time, median survival time and treatment safety of tumor-bearing mice were observed. Immunohistochemistry, multiple immunofluorescence and flow cytometry were used to detect the expression of tumor-associated microangiogenesis molecules (CD34), lymphatic microvessels (LYVE-1), collagen fibers and immune cell phenotypes (CD3, CD4, CD8, Treg and PD1). Results: High fat and low carbohydrate diet combined with radiotherapy (45F+RT) group had the best tumor control, and the tumor volume was significantly smaller than the control group (p &lt; 0.001), and tumor weight in the combined treatment group (45F+RT) was significantly lower than that in the normal diet (PT, fat 12.11% of energy) and 45F group (p &lt; 0.001); The blood glucose in 45F group was lower than that in PT group, but there was no statistical difference (p &lt; 0.05); It was found that the βHB value in the high-fat and low-carbohydrate diet group was higher than that in the normal diet group. There were statistically significant differences in the second and third weeks (1.00±0.20mmol/L vs 0.63±0.06mmol/L, 0.90±0.17mmol/L vs 0.70±0.10mmol/L, p &lt; 0.05). The median survival time of mice in each group was 38 days in the PT group, 55 days in the PT+RT group and 41 days in the 45F group, but not in the 45F+RT group. Immunohistochemistry and Multiple immunofluorescence showed that CD8 expression was up-regulated and PD1, CD34, LYVE-1 and collagen fiber expression were down-regulated in 45F+RT group. Flow cytometry showed that the proportion of CD8+T cells in 45F+RT group was higher than that in PT group and PT+RT group (p &lt; 0.05) and higher than 45F group, but the difference was not statistically significant (p &lt; 0.05); The proportion of CD4+T cells in PT+RT and 45F+RT groups was higher than that in PT and 45F groups (p &lt; 0.05); The proportion of Treg in T cells in 45F+RT group was lower than that in PT+RT group, but the difference was not statistically significant (p &lt; 0.05). Conclusions: High fat and low carbohydrate diet combined with radiotherapy can enhance the recruitment and function of immune effector cells in tumor microenvironment and inhibit tumor microangiogenesis, thereby inhibiting tumor growth.
REFLECTions on Combination Therapies Empowered by Data Sharing
Authors: Trevor J. Pugh, Benjamin Haibe-Kains
Journal: Cancer Discovery (2022)

Summary: Li and colleagues present REFLECT, a computational approach to precision oncology that nominates effective drug combinations by utilizing a diverse compendium of publicly available preclinical and clinical genomic, transcriptomic, and proteomic data. The preliminary validation of the REFLECT system in preclinical and clinical trial settings showcases potential for clinical implementation, although challenges remain. See related article by Li et al., p. 1542 (4).
IMG-03. Impact of childhood cerebellar tumor surgery on cognition: Can fMRI serve as a surrogate marker?
Authors: Christian Dorfer, Thomas Pletschko, Rene Seiger, Monika Chocholous, Gregor Kasprian, Karl Roessler, Kathrin Kollndorfer, Veronika Schöpf, Ulrike Leiss, Irene Slavc, Daniela Prayer, Rupert Lanzenberger, Thomas Czech
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Childhood cerebellar pilocytic astrocytomas harbour excellent overall survival rates after surgical resection, but the patients may exhibit specific cognitive and behavioural problems emphasising our current understanding of the cerebellar role in cognition. Functional MRI has catalysed the mechanistic insights into brain functional systems and has already been linked with the neuropsychological performance. We aimed to exploit the question whether functional MRI can be used as a surrogate measure for the cognitive outcome assessment of these patients. METHODS: We investigated 13 patients (median age 22.0 years, range 15.2 – 31.7) after a median interval between surgery and examination of 15.0 years (range 4.2 – 20.8) and 16 matched controls. All subjects underwent a functional 3T MRI scans in a resting state condition and a battery neuropsychological tests. RESULTS: Patients showed a significantly increased functional connectivity in the precuneus compared to controls (p&amp;lt;0.05) and at the same time impairments in various domains of neuropsychological functioning such as a lower mean WIE IQ percentile (M = 48.62, SD = 29.14), lower scores in the TMT letter sequencing (M = 49.54, SD = 30.66), worse performance on the WIE subtest Digit Symbol Coding (M = 38.92, SD = 35.29), subtest Symbol Search (M = 40.75, SD = 35,28), and TAP divided attention task (M = 783.92, SD = 73.20). CONCLUSION: Functional MRI has the potential to serve as a surrogate measure for the cognitive outcome assessment. The precuneus brain region is heavily involved in the cerebral associative oversight of cerebellar cognitive function.
What Overturning <i>Roe v Wade</i> May Mean for Assisted Reproductive Technologies in the US
Authors: I. Glenn Cohen, Judith Daar, Eli Y. Adashi
Journal: JAMA (2022)

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The role of RARRES2 in regulating lipic metabolic reprogramming in the development of brain metastases in triple negative breast cancer.
Authors: Yiqun Li, Fangzhou Sun, Chunxiao Li, Hongnan Mo, Haili Qian, Fei Ma
Journal: Journal of Clinical Oncology (2022)

e13047 Background: Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastases (BM) and a poor prognosis. As the most lethal form of breast cancer, brain metastases remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastases (BCBM), but the underlying mechanisms are far from been fully elucidated. Methods: Using public datasets and our single-cell transcriptome sequencing data, we identified and verified the specific down-regulation of RARRES2, a multifunctional adipokine and chemokine, in brain metastases of triple negative breast cancer. We investigated the effect of aberrant RARRES2 expression on brain metastases in both in vitro and in vivo studies. Key signaling pathway components were evaluated using qPCR and Western blot analysis. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2. Results: We show for the first time that down-regulation of RARRES2 is specifically associated with BCBM, and that RARRES2 promoted BCBM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain-tropic triple negative breast cancer cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols (TAGs) by regulating PTEN-PI3K-SREBP1 signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment. Conclusions: Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of brain metastases, thereby offering potential therapeutic targets for BCBM in TNBC.
The potential role of Monocyte Distribution Width (MDW) as early post-operative sepsis biomarker
Authors: D. Baiamonte, S. Altomare, R. Giaimo, M. Vella, P. Mannone, M. Pinelli, G. Tulone, L. Agnello, M. Vidali, B. Lo Sasso, R.V. Giglio, C.M. Gambino, N. Pavan, M. Ciaccio, A. Simonato
Journal: European Urology (2022)
Addendum. 10. Cardiovascular Disease and Risk Management: <i>Standards of Medical Care in Diabetes—2022</i>. Diabetes Care 2022;45(Suppl. 1):S144–S174
Journal: Diabetes Care (2022)

Section 10, Cardiovascular Disease and Risk Management, of the Standards of Medical Care in Diabetes-2022 has been annotated to include evidence from trials of medication effects in patients with type 2 diabetes on heart failure, cardiovascular, and chronic kidney disease outcomes including Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved), Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF), Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD), and Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD), and to remove information associated with the discontinued trial Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes (PROMINENT).The online version of the article (
A novel EAU Guidelines based clinicial decision support software – evaluation of Siemens AIPC Software in prostate cancer screening
Authors: C. Wetterauer, T. Horn, M. Henkel, F. Leboutte, P. Trotsenko, S. Dugas, S. Sutter, G. Ficht, C. Engesser, M. Matthias, J. Ebbing, B. Stieltjes, P. Cornford, H.H. Seifert, A. Stalder
Journal: European Urology (2022)